Mitoguazone induces apoptosis via a p53-independent mechanism.
Mitoguazone induces apoptosis via a p53-independent mechanism.
复制标题
Mitoguazone 通过 p53 独立机制诱导细胞凋亡。
DOI：
10.1097/00001813-199808000-00009
复制
发表时间：
1998
影响因子：
2.3
通讯作者：
D. V. Von Hoff
中科院分区：
文献类型：
--
作者：
K. Davidson;T. Petit;E. Izbicka;S. Koester;D. V. Von Hoff
Mitoguazone（甲基乙二醛双胍酰腙，甲基-GAG或MGBG）是一种合成的多羰基衍生物，对霍奇金淋巴瘤和非霍奇金淋巴瘤、头颈癌、前列腺癌和食管癌患者具有活性。Mitoguazone最近也被证明对艾滋病相关淋巴瘤患者有活性。在抗癌药物中，米托胍酮通过干扰多胺生物合成途径而具有独特的作用机制。多胺通过在相对链上的磷酸基团之间的非共价交联来稳定DNA结构。此外，mitoguazone引起氧化磷酸化解偶联。在这项研究中，在三个伯基特淋巴瘤细胞系（Raji、拉莫斯和Daudi）和一个前列腺癌细胞系（MPC 3）中评估了米托胍酮通过抑制多胺途径诱导细胞凋亡的能力。在两种人乳腺癌细胞系（具有野生型p53的MCF 7和具有突变的p53的VM 4K）中进行另外的评价，以确定p53肿瘤抑制基因是否是有效的细胞凋亡诱导所需的。本研究表明，mitoguazone诱导细胞凋亡的所有不同的人癌细胞系中测试的浓度和时间依赖性的方式，并触发p53非依赖性程序性细胞死亡的人乳腺癌MCF 7细胞系。
Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl derivative with activity in patients with Hodgkin's and non-Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer. Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism of action via interference with the polyamine biosynthetic pathway. Polyamines stabilize DNA structure by non-covalent cross-bridging between phosphate groups on opposite strands. In addition, mitoguazone causes uncoupling of oxidative phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Additional evaluations were performed in two human breast cancer cell lines (MCF7 with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor suppressor gene was required for efficient apoptosis induction. The present study demonstrated that mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.